Diagnostic Assessment: Iron-Deficiency Anemia vs. Thalassemia Trait
This 15-year-old female has iron-deficiency anemia, not thalassemia trait, based on her elevated RDW (16.6%) combined with severe microcytosis (MCV 66.2 fL), low serum iron (45 µg/dL), and elevated ESR (36 mm/hr) suggesting inflammation or blood loss. 1
Key Diagnostic Reasoning
The elevated RDW (16.6%) is the critical discriminating feature. A low MCV with RDW >14.0% strongly indicates iron-deficiency anemia, whereas thalassemia minor typically presents with RDW ≤14.0% because red cells are more uniform in thalassemia. 1 While approximately half of thalassemia cases can show elevated RDW, the combination of elevated RDW with low serum iron (45 µg/dL) and elevated ESR (36 mm/hr) makes iron deficiency the primary diagnosis. 2
The elevated ESR (36 mm/hr) suggests either chronic blood loss, inflammation, or both—findings not typical of pure thalassemia trait but consistent with iron deficiency from menstrual blood loss or gastrointestinal bleeding. 1, 3
Required Laboratory Confirmation
Order serum ferritin immediately as the single most powerful test for confirming iron deficiency. 4, 5, 6
- Ferritin <15 µg/L confirms absent iron stores with 99% specificity 4
- Ferritin <30 µg/L indicates low body iron stores 4
- Ferritin <45 µg/L provides optimal sensitivity and specificity in routine practice 4
Measure transferrin saturation (TSAT) concurrently because the elevated ESR indicates inflammation, which can falsely elevate ferritin. 4 TSAT <16-20% confirms iron deficiency even when ferritin appears normal due to inflammation. 1, 4
If ferritin is normal or borderline (>30 µg/L), order hemoglobin electrophoresis to definitively exclude beta-thalassemia trait, which shows elevated HbA2 >3.5%. 4, 6 However, given the elevated RDW and low serum iron, thalassemia is unlikely.
Investigation of Underlying Cause
In adolescent females, the two most common causes are heavy menstrual bleeding and gastrointestinal blood loss. 4 The elevated ESR raises concern for occult GI pathology beyond simple menstrual loss.
Mandatory evaluation includes:
- Detailed menstrual history: quantify bleeding (number of pads/tampons per day, clots, duration) 4
- Gastrointestinal symptoms: melena, hematochezia, abdominal pain, change in bowel habits 4
- Dietary assessment: inadequate iron intake, vegetarian diet 1, 6
- Celiac disease screening (tissue transglutaminase antibodies) because celiac accounts for 2-3% of iron-deficiency anemia cases and causes malabsorption 4
If menstrual history does not fully explain the severity of anemia, or if any GI symptoms are present, gastrointestinal evaluation with upper endoscopy and colonoscopy is required to exclude malignancy, inflammatory bowel disease, or celiac disease. 4 The elevated ESR particularly warrants investigation for inflammatory or neoplastic processes.
Immediate Treatment
Start oral iron supplementation immediately while diagnostic workup proceeds. 4 Prescribe ferrous sulfate 200 mg (65 mg elemental iron) three times daily. 4 Alternative formulations include ferrous gluconate or ferrous fumarate if ferrous sulfate causes intolerable gastrointestinal side effects. 4
A hemoglobin rise ≥10 g/L within 2 weeks confirms iron deficiency as the diagnosis. 4 This therapeutic response is diagnostic even when iron studies are equivocal. 4
Continue iron supplementation for at least 3 months after hemoglobin normalizes to replenish iron stores. 4, 7
Monitoring Protocol
- Recheck hemoglobin and red cell indices at 2 weeks to confirm response (expected rise ≥10 g/L) 4
- Monitor at 3-month intervals for one year, then annually 4
- Provide additional oral iron if hemoglobin or MCV falls below normal 4
Critical Pitfalls to Avoid
Do not assume all microcytic anemia in adolescents is benign iron deficiency from menstruation. The elevated ESR (36 mm/hr) mandates investigation for inflammatory bowel disease, celiac disease, or occult malignancy if menstrual loss does not fully account for the severity. 4, 3
Do not order hemoglobin electrophoresis before checking iron studies. Hemoglobin electrophoresis is only indicated when iron studies are normal or borderline, or when the patient fails to respond to adequate iron therapy after 4 weeks. 4, 6
Do not overlook combined deficiencies. Iron deficiency can coexist with vitamin B12 or folate deficiency; the elevated RDW (16.6%) may signal combined micronutrient deficiencies. 4
If the patient fails to respond to oral iron within 2-4 weeks despite good compliance, consider: 4, 6
- Ongoing blood loss exceeding replacement
- Malabsorption (celiac disease, H. pylori gastritis, inflammatory bowel disease)
- Rare genetic disorders (iron-refractory iron deficiency anemia/IRIDA)
- Incorrect diagnosis (thalassemia, anemia of chronic disease, sideroblastic anemia)